Boesenbergia stenophylla-derived Stenophyllol B exerts antiproliferative and oxidative stress responses in triple-negative breast cancer cells with few side effects in normal cells
Triple-negative breast cancer (TNBC) is insensitive to target therapy for non-TNBC and needs novel drug discovery. Extracts of the traditional herb Boesenbergia plant in Southern Asia exhibit anticancer effects and contain novel bioactive compounds but merely show cytotoxicity. We recently isolated...
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my.um.eprints.382702023-07-07T08:06:30Z http://eprints.um.edu.my/38270/ Boesenbergia stenophylla-derived Stenophyllol B exerts antiproliferative and oxidative stress responses in triple-negative breast cancer cells with few side effects in normal cells Lee, Min-Yu Shiau, Jun-Ping Tang, Jen-Yang Hou, Ming-Feng Primus, Phoebe Sussana Kao, Chai-Lin Choo, Yeun Mun Chang, Hsueh-Wei QD Chemistry QH301 Biology Triple-negative breast cancer (TNBC) is insensitive to target therapy for non-TNBC and needs novel drug discovery. Extracts of the traditional herb Boesenbergia plant in Southern Asia exhibit anticancer effects and contain novel bioactive compounds but merely show cytotoxicity. We recently isolated a new compound from B. stenophylla, stenophyllol B (StenB), but the impact and mechanism of its proliferation-modulating function on TNBC cells remain uninvestigated. This study aimed to assess the antiproliferative responses of StenB in TNBC cells and examine the drug safety in normal cells. StenB effectively suppressed the proliferation of TNBC cells rather than normal cells in terms of an ATP assay. This preferential antiproliferative function was alleviated by pretreating inhibitors for oxidative stress (N-acetylcysteine (NAC)) and apoptosis (Z-VAD-FMK). Accordingly, the oxidative-stress-related mechanisms were further assessed. StenB caused subG1 and G2/M accumulation but reduced the G1 phase in TNBC cells, while normal cells remained unchanged between the control and StenB treatments. The apoptosis behavior of TNBC cells was suppressed by StenB, whereas that of normal cells was not suppressed according to an annexin V assay. StenB-modulated apoptosis signaling, such as for caspases 3, 8, and 9, was more significantly activated in TNBC than in normal cells. StenB also caused oxidative stress in TNBC cells but not in normal cells according to a flow cytometry assay monitoring reactive oxygen species, mitochondrial superoxide, and their membrane potential. StenB induced greater DNA damage responses (?H2AX and 8-hydroxy-2-deoxyguanosine) in TNBC than in normal cells. All these StenB responses were alleviated by NAC pretreatment. Collectively, StenB modulated oxidative stress responses, leading to the antiproliferation of TNBC cells with little cytotoxicity in normal cells. MDPI 2023-04 Article PeerReviewed Lee, Min-Yu and Shiau, Jun-Ping and Tang, Jen-Yang and Hou, Ming-Feng and Primus, Phoebe Sussana and Kao, Chai-Lin and Choo, Yeun Mun and Chang, Hsueh-Wei (2023) Boesenbergia stenophylla-derived Stenophyllol B exerts antiproliferative and oxidative stress responses in triple-negative breast cancer cells with few side effects in normal cells. International Journal of Molecular Sciences, 24 (9). ISSN 1661-6596, DOI https://doi.org/10.3390/ijms24097751 <https://doi.org/10.3390/ijms24097751>. 10.3390/ijms24097751 |
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QD Chemistry QH301 Biology Lee, Min-Yu Shiau, Jun-Ping Tang, Jen-Yang Hou, Ming-Feng Primus, Phoebe Sussana Kao, Chai-Lin Choo, Yeun Mun Chang, Hsueh-Wei Boesenbergia stenophylla-derived Stenophyllol B exerts antiproliferative and oxidative stress responses in triple-negative breast cancer cells with few side effects in normal cells |
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Triple-negative breast cancer (TNBC) is insensitive to target therapy for non-TNBC and needs novel drug discovery. Extracts of the traditional herb Boesenbergia plant in Southern Asia exhibit anticancer effects and contain novel bioactive compounds but merely show cytotoxicity. We recently isolated a new compound from B. stenophylla, stenophyllol B (StenB), but the impact and mechanism of its proliferation-modulating function on TNBC cells remain uninvestigated. This study aimed to assess the antiproliferative responses of StenB in TNBC cells and examine the drug safety in normal cells. StenB effectively suppressed the proliferation of TNBC cells rather than normal cells in terms of an ATP assay. This preferential antiproliferative function was alleviated by pretreating inhibitors for oxidative stress (N-acetylcysteine (NAC)) and apoptosis (Z-VAD-FMK). Accordingly, the oxidative-stress-related mechanisms were further assessed. StenB caused subG1 and G2/M accumulation but reduced the G1 phase in TNBC cells, while normal cells remained unchanged between the control and StenB treatments. The apoptosis behavior of TNBC cells was suppressed by StenB, whereas that of normal cells was not suppressed according to an annexin V assay. StenB-modulated apoptosis signaling, such as for caspases 3, 8, and 9, was more significantly activated in TNBC than in normal cells. StenB also caused oxidative stress in TNBC cells but not in normal cells according to a flow cytometry assay monitoring reactive oxygen species, mitochondrial superoxide, and their membrane potential. StenB induced greater DNA damage responses (?H2AX and 8-hydroxy-2-deoxyguanosine) in TNBC than in normal cells. All these StenB responses were alleviated by NAC pretreatment. Collectively, StenB modulated oxidative stress responses, leading to the antiproliferation of TNBC cells with little cytotoxicity in normal cells. |
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Lee, Min-Yu Shiau, Jun-Ping Tang, Jen-Yang Hou, Ming-Feng Primus, Phoebe Sussana Kao, Chai-Lin Choo, Yeun Mun Chang, Hsueh-Wei |
author_facet |
Lee, Min-Yu Shiau, Jun-Ping Tang, Jen-Yang Hou, Ming-Feng Primus, Phoebe Sussana Kao, Chai-Lin Choo, Yeun Mun Chang, Hsueh-Wei |
author_sort |
Lee, Min-Yu |
title |
Boesenbergia stenophylla-derived Stenophyllol B exerts antiproliferative and oxidative stress responses in triple-negative breast cancer cells with few side effects in normal cells |
title_short |
Boesenbergia stenophylla-derived Stenophyllol B exerts antiproliferative and oxidative stress responses in triple-negative breast cancer cells with few side effects in normal cells |
title_full |
Boesenbergia stenophylla-derived Stenophyllol B exerts antiproliferative and oxidative stress responses in triple-negative breast cancer cells with few side effects in normal cells |
title_fullStr |
Boesenbergia stenophylla-derived Stenophyllol B exerts antiproliferative and oxidative stress responses in triple-negative breast cancer cells with few side effects in normal cells |
title_full_unstemmed |
Boesenbergia stenophylla-derived Stenophyllol B exerts antiproliferative and oxidative stress responses in triple-negative breast cancer cells with few side effects in normal cells |
title_sort |
boesenbergia stenophylla-derived stenophyllol b exerts antiproliferative and oxidative stress responses in triple-negative breast cancer cells with few side effects in normal cells |
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MDPI |
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2023 |
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http://eprints.um.edu.my/38270/ |
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1772811753099362304 |
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13.19449 |